X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.
Pubmed ID: 9489700 RIS Download
Mesh terms: Amino Acid Sequence | Base Sequence | Brain | Cerebral Cortex | Chromosome Fragility | Chromosome Mapping | DNA, Complementary | Epilepsy | Family Health | Genes | Humans | Microtubule-Associated Proteins | Molecular Sequence Data | Mutation | Neuropeptides | Protein-Serine-Threonine Kinases | Proteins | Sequence Homology, Amino Acid | Sex Chromosome Aberrations | Signal Transduction | Syndrome | Translocation, Genetic | X Chromosome
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